TH 2.2 is a cloned hybrid B lymphocyte line which is induced by bacterial lipopolysaccharide (LPS) to secretion of IgM and the cytokines GM-CSF, IL-3, and IL-6. LPS also markedly inhibits growth of TH 2.2 both in bulk and in clonal culture. Pretreatment of TH 2.2 with 1 or 5 microg/ml of LPS prevents inhibition of growth by subsequent treatment. Responses recover, but require long term passage to do so. Almost all fresh clones of TH 2.2 are sensitive to LPS. Repeated analysis of >60 clones showed that occasional resistance appeared in one passage generation only in 10- 15%, and disappeared with subsequent testing. Resistance could be induced in stably sensitive clones of TH 2.2 by treatment with LPS. About 1/3rd of 90 clones from cells pretreated with 1 or 5 microg LPS were fully resistant when first tested. The majority of these clones became slowly sensitive with subsequent passage; 4 have remained resistant, but at lower levels than initially, and four partially resistant clones have remained partially resistant. The effects of pretreatment on cytokine secretion are more complicated: TH 2.2 in short term passage is rendered unresponsive (marked reduction in secretion) by pretreatment; cells in long term passage are rendered hyper-responsive in this respect. In either case, the cells return to normal with long enough further passage.